Skin cancer is the most commonly diagnosed cancer in the United States. Malignant melanoma is the most lethal form of skin cancer and the most commonly diagnosed malignancy among young adults with an increasing incidence. It was predicted that there would be 62,940 cases of malignant melanoma newly reported and 8,420 fatalities in 2008 (1). Melanoma metastases are highly aggressive and the survival time for patients with metastatic melanoma averages 3-15 months (2). Unfortunately, no curative treatment exists for metastatic melanoma. Early diagnosis and prompt surgical removal are a patient's best opportunity for a cure. Single photon emission tomography (SPECT) and positron emission tomography (PET) techniques are attractive non-invasive imaging modalities due to their high sensitivity (10−10 to 10−11 M for SPECT and 10−11 to 10−12 M for PET) and spatial resolution (1-2 mm) (3, 4). Currently, 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET imaging is commonly used for the diagnosis and staging of melanoma. However, [18F]FDG is not a melanoma-specific imaging probe since the elevated uptake of [18F]FDG in tumor is due to the higher metabolism and energy consumption in tumor cells than that in normal cells. [18F]FDG PET imaging only detects 23% melanoma metastases smaller than 5 mm (5). Meanwhile, some melanoma cells are not detected by [18F]FDG PET imaging since they use substrates other than glucose as energy sources (6, 7). Therefore, it is highly desirable to develop novel effective imaging probes to detect primary, metastatic and recurrent melanomas.